1. Field of the Invention
The present invention relates to optical measurement devices configured to carry out optical measurements by utilizing nonlinear optical phenomena; embodiments of the invention also relate to light source adjustment units and wavelength adjustment programs that are used in the optical measurement devices, and to subject information obtaining systems.
2. Description of the Related Art
In recent years, spectrometric devices that utilize nonlinear optical phenomena have been developed and used for observing small-sized organisms. Known spectroscopic techniques that utilize nonlinear optical phenomena include sum frequency generation spectroscopy and two-photon absorption spectroscopy. The use of such techniques makes it possible to observe unstained biological tissues.
In addition, optical measurement devices that utilize a phenomenon referred to as nonlinear Raman scattering, such as coherent anti-Stokes Raman scattering and stimulated Raman scattering, to obtain vibration information of molecules are being developed. In particular, optical measurement devices that utilize nonlinear Raman scattering phenomena (hereinafter, also referred to as nonlinear Raman scattering optical measurement devices) are expected to serve as devices for observing a substance distribution within a cell. It should be noted that, in the present invention and in the present specification, an optical measurement device corresponds to any device that carries out optical measurement, and examples of such a device include a device for measuring an optical spectrum and an optical microscope for carrying out optical observation.
In a nonlinear Raman scattering optical measurement device, a subject is irradiated with two laser beams having different wavelengths in such a manner that the laser beams form focuses within the subject. When a difference between the frequencies of the two laser beams coincides with the frequency of the molecular vibration of the molecules within the subject, the frequency of the molecular vibration of the molecules within the subject can be obtained by utilizing nonlinear Raman scattering phenomena in which scattering occurs specifically at the location(s) where the laser beams are focused. By detecting a change in the intensity of the scattered light while varying a difference between the frequencies of the incident laser beams, a Raman spectrum can be obtained. International Publication No. WO2010/140614 A1 and Brian G Saar et al., “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering”, Science, vol. 330, No. 6009, 1368-1370 (2010) disclose techniques for obtaining a spatial distribution of a Raman spectrum at high speed while sweeping a wavelength at high speed in a stimulated Raman scattering optical measurement device.
Furthermore, sum frequency generation, difference frequency generation, two-photon fluorescence, two-photon absorption, multiphoton absorption, and other similar techniques are known as nonlinear optical phenomena where a dual-wavelength laser beam is used. In an optical measurement device that utilizes such phenomena, or in sum frequency generation spectroscopy, for example, a subject is irradiated with two laser beams having different frequencies and sum frequency light generated within the subject at that time is detected. This is effectively used for imaging cytoplasm or the like, while utilizing extremely high interface selectivity. In addition, while two-photon absorption spectroscopy utilizes a phenomenon in which two photons are absorbed simultaneously to shift to an excited state, in a case of dual-wavelength excitation in particular, light having a frequency that is equal to the sum of the frequencies of the incident two laser beams is detected. This allows light having a long wavelength to be used as incident light and is thus effectively used to observe, in particular, a relatively deep portion within an organism.
In optical measurement utilizing nonlinear optical phenomena, a spectrum is often expressed by using a wave number. As known by persons skilled in the art, the term “wave number” (also sometimes referred to as “wavenumber”) is the reciprocal of the wavelength expressed in centimeters (cm), and represents a measure of the frequency of radiation. More generally, wavenumber=1/λ is the measurement of the number of wavelengths per unit distance, where λ is the wavelength. In the present invention and in the present specification, a wave number to be used for measurement in optical measurement utilizing nonlinear optical phenomena is referred to as a measurement wave number. In other words, in optical measurement utilizing nonlinear Raman scattering phenomena or difference frequency generation, a measurement wave number corresponds to a difference between the wave numbers of two laser beams with which a subject is irradiated. Meanwhile, in optical measurement utilizing sum frequency generation, two-photon absorption, or multiphoton absorption, a measurement wave number corresponds to a sum of the wave numbers of two or more laser beams with which a subject is irradiated.